Consequences of introducing a disulfide bond into an antibacterial and hemolytic peptide

The effect of introducing a disulfide bridge between the N- and C-terminal ends on the structure and biological activities of the 13-residue linear pe ptide PKLLKTFLSKWIG(SPFK), which has both antibacterial and hemolytic activ ity, have been investigated. The terminal amino acids P and G in SPFK were replaced by cysteines to form a disulfide bridge. The linear peptides C(Acm )KLLKTFLSKWIC(Acm) and C(Acm) KLLKTFLSKW1C(Acm)-amide, where Acm is acetami domethyl group, showed antibacterial activity but did nor possess hemolytic activity unlike SPFK. Introduction of an S-S bridge resulted in enhanced h emolytic activity compared with SPFK. The hemolytic activity was particular ly pronounced in the cyclic peptide CKLLKTFLSKWIC-amide Circular dichroism studies indicate that the cyclic peptides tend to adopt distorted helical s tructures. The cyclic peptides also have a greater affinity for lipid vesic les, which could be the reason For the effective perturbation of the erythr ocyte membrane.